Delving into the Latest Updates on VU6019278 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

mGluR7

Action

positive allosteric modulator

Mechanism

mGluR7 positive allosteric modulator(Metabotropic glutamate receptor 7 positive allosteric modulator)

Therapeutic Areas

Neoplasms

Active Indication-

Inactive Indication

Neoplasms

Originator Organization

Vanderbilt University

Active Organization-

Inactive Organization

Vanderbilt University

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC20H15F3N4O4

InChIKeyQDBAGSYNQOBNDU-UHFFFAOYSA-N

CAS Registry2351146-77-3

We describe here a series of metabotropic glutamate receptor 7 (mGlu₇) negative allosteric modulators (NAMs) with a saturable range of activity in inhibiting responses to an orthosteric agonist in two distinct in vitro pharmacological assays. The range of inhibition among compounds in this scaffold provides highly structurally related ligands with differential degrees of receptor blockade that can be used to understand inhibitory efficacy profiles in native tissue or in vivo.

01 May 2019·Bioorganic & Medicinal Chemistry LettersQ4 · MEDICINE

Surveying heterocycles as amide bioisosteres within a series of mGlu7 NAMs: Discovery of VU6019278

Q4 · MEDICINE

Article

Author: Conn, P Jeffrey ; Blobaum, Anna L ; Lindsley, Craig W ; Engers, Darren W ; Niswender, Colleen M ; Quitlag, Marc C ; Reed, Carson W ; Jenkins, Matthew T ; Washecheck, Jordan P ; Rodriguez, Alice L

This letter describes a diversity-oriented library approach to rapidly assess diverse heterocycles as bioisosteric replacements for a metabolically labile amide moiety within a series of mGlu₇ negative allosteric modulators (NAMs). SAR rapidly honed in on either a 1,2,4- or 1,3,4-oxadizaole ring system as an effective bioisostere for the amide. Further optimization of the southern region of the mGlu₇ NAM chemotype led to the discovery of VU6019278, a potent mGlu₇ NAM (IC₅₀ = 501 nM, 6.3% L-AP₄ Min) with favorable plasma protein binding (rat f_u = 0.10), low predicted hepatic clearance (rat CL_hep = 27.7 mL/min/kg) and high CNS penetration (rat K_p = 4.9, K_p,uu = 0.65).

100 Deals associated with VU6019278

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